Inhibition of protein arginine deiminase II suppresses retinoblastoma in orthotopic transplantation in mice

Sojin Kim, Yong Keun Song, Chang Sik Cho, Hyo Jung Kim, Sungsoon Fang, Dong Hyun Jo, Hyunkyung Kim

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Chemotherapies are used for treating retinoblas‑ toma; however, numerous patients suffer from recurrence or symptoms due to chemotherapy, which emphasizes the need for alternative therapeutic strategies. The present study demonstrated that protein arginine deiminase Ⅱ (PADI2) was highly expressed in human and mouse retinoblastoma tissues due to the overexpression of E2 factor (E2F). By inhibiting PADI2 activity, the expression of phosphorylated AKT was reduced, and cleaved poly (ADP‑ribose) polymerase level was increased, leading to induced apoptosis. Similar results were obtained in orthotopic mouse models with reduced tumor volumes. In addition, BB‑Cl‑amidine showed low toxicity in vivo. These results suggested that PADI2 inhibition has potential clinical translation. Furthermore, the present study highlights the potential of epigenetic approaches to target RB1‑deficient mutations at the molecular level. The current findings provide new insights into the importance of retino‑ blastoma intervention by managing PADI2 activity according to the treatment of specific inhibitors and depletion approaches in vitro and in orthotopic mouse models.

Original languageEnglish
Article number146
JournalOncology reports
Volume50
Issue number1
DOIs
Publication statusPublished - 2023

Bibliographical note

Publisher Copyright:
Copyright © 2023 Kim et al. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) License.

Keywords

  • AKT phosphorylation
  • BB‑Cl‑amidine
  • E2 factor
  • protein arginine deiminase II
  • retinoblastoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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